Ischemic heart disease Ischemia => imbalance between oxygen demands and oxygen supply

Number 1 cause of death in males and female in USA and developped -  Demands
countries
-  O2 supply
Definition :
Most important cause : Atheromatous plaque fibro fatty plaque formed in
A group of clinical pathological syndroms which result from an imbalance intima
in oxygen supply and demand in myocardium => relative ischemia in the
Precursor lesions start forming very early at 10 years
myocardium
But clinically start manifestation > 40 years
Ischemia Vs hypoxemia : ischemia more dangerous
Dysfunctional endothelium
Ischemia Hypoxemia
Reduced blood flow => 3 features Blood flow is normal, there is only : Fibrous cap : smooth muscle releasing extra c matrix + collagen +
- oxygen supply oxygen supply: examples macrophages
-  nutrients - severe anemia
-  washout of metabolic waste - severe pulmonary disease (blood is Foam cells : (Smooth muscles + macrophages) eating lipids
not getting oxygenated well)
- cyanotic heart disease Lipid core

Neo vascularisation
Mechanisms of myocardial ischemia
Atheromatous plaque can be :
Note : Ischemic heart disease 99% involve left ventricle
- stable uncomplicated
RV LV
Thin => less O2 demand Thick => O2 demand - unstable, going through acute changes and thus vulnerable to
Generates less tension in wall 0=> 25 Generates higher pressure 0 => complications (disruption is one of them)
- less work 125
Squeezes his own micro circulation - work Stable Unstable vulnerable
with less tension Squeezes his own micro circulation Fibrous cap Thick Thin
with more tension (impedes it) Form cells Less More
-  O2 supply No blood flow during systole Macrophages ( metalloproteases) Less More
-  O2 supply Fat Less More
Receives blood supply during Receives blood supply during
Systole and diastole diastole only.
Unless it is hypertrophied
 Stable Unstable, vulnerable to acute disruption - blood comin from the coronary lumeng
- fixed obstruction to It may undergo :
blood flow it can’t dilate 1- Erosion, ulceration 4. vasoconstriction (TxA2)
- growing over years 2- Fissuring, rupture 5. atheroembolism : a part of atheroma (lipid + cells => mass) disrupt and
- if > 70% luminal 1+2 => thrombus formation (physiologic block a blood vessel
obstruction => ischemia thrombolysis, progression or embolism)
only if increased demand 3- Intra plaque hemoorhage Statins
of O2 : tachycardia, 4- Vasoconstriction
hypertension 5- Athero-embolism - reduce cholesterol levels => less cholesterol supply to plaque
- if > 90% obstruction =>
ischemia even during rest - anti inflammatory action on the plaque => inhibit inflammatory activity
in the plaque => less macrophages => les metalloproteases => fibrous cap
no more digested => stabilizing the plaque
40 % obstruction plaque but having dynamic changes => more dangerous
than a stable 80% obstruction plaque Platelet adhesion => dynamic plaque

Unstable plaque :
Smoking favors platelet adhesion to disrupted plaque
It may undergo :
1- erosions /ulceration => endothelium damage => expose the basement Smoking : favors
membrane( intact) which is thrombogenic
- Plaque formation
2- fissuring/ rupture (if big area) => deeper damage => exposing lipid
material which is highly thrombogenic - Platelet adhesion to the plaque and thrombus formation
In both 1+2 conditions => platelet adhesion, activation (release) and
aggregation => thrombus formation : coagulation : conversion of soluble If someone stops smoking => within 1 year => chances to MI reduced to
fibrinogen to insoluble fibrin 30% by reducing platelet stickability

Thrombus can
- physiologic thrombolysis
- grow more Platelets release TxA2 => vasoconstrictor => bad news => dynamic
- detaches and causes embolism changes

Most vulnerable part of the cap to rupture => the edges (ends) of the cap
where it meets the normal endothelium
Atherosclerosis in coronary artery => coronary artery disease CAD

3-Intra plaque hemorrhage baloonisation => acute obstruction

- weakness of new vascularisation

Acute changes that occur in a vulnerable plaque can be enhanced by some Ischemic heart disease
factors making it a more vulnerable plaque :
Causes of ischemic heart diseases
Extrinsic : smoking
 O2 supply  O2 demand
Intrinsic : tachycardia 1- Atheroma 1- LVH (AS, high BP, AR,
2- Coronary ostial stenosis HOCM) :
- tachycardia, 3- Aortic dissection  risk of infarctions but
4- Coronary vasculitis :  risk for rupture of
More O2 demand, soft plaque has more chances to be disrupted because of polyarthritis nodosa, Kawasaki infarctions because it s a
tachycardia (high blood pressure) disease thick wall
5- Coronary artery embolism : IE, 2-  HR => tachycardia =>
-MI in the morning 6 to 8 a.m dilated LA (MS, MR, AFib) Fat  diastole duration which
embolism is perfusion time of
Adrenaline increases platelet stickability after awakening 6- Polycytemia myocardium and it makes
7- Severe prolonged hypotension atheromatous plaque
Acute coronary syndroms
8- Syndrome X more vulnerable to acute
1- Instable angina changes ( exertion,
9- Severe anemia emotional stress)
2- Acute myocardial infarction 10- Carboxyhemoglobinemia 3- hyperthyroidism =>
3- Sudden cardiac death 11- Severe chronic lung disease increase metabolism
more common in the morning, 4- pregnancy (twins)
more common in patients with inflammatory plaque 5- HTAP => risk of right
heart infarctions
You would like to know the risk of having a MI in these patients
Total occlusion of coronary artery
Angina => MI or MI => recurrent MI
Myocardial cells death start time => 20 – 40 minutes
=> determine inflammatory activity in the plaque
Continues up to 6 – 12 hours
More inflammatory activity n the plaque => more chances for acute
changes => more risk to develop MI Aortic stenosis :

CRP : simple way LV Hypertrophied more O2 demand

Inflammatory cells release cytokins ===> hepatocytes which release CRP Vessels squeezd more

CRP  => high chance to MI Stenosis => pressure in root of aorta is less
 O2 supply 10) Prolonged severe hypotension : during operation when he wakes up
infracted or developed stroke
1) Athroma : coronary artery disease ===> risk factors in the other Hypotension => reduce perfusion
lecture The deepest layer of myocardium (sub endocardial) is more
- stable plaque vulnerable to ischemia
- disrupted plaque : erosion / ulceration, If the patient survives to MI because of hypotension => partial
fissure/ rupture => platelet plug formation, circumflention infarction (sub endocardial myocardium)
thrombus, vasoconstriction
intra plaque hemoorhage 11) Syndrome X : very resistant to treatment
2) Coronary ostial stenosis : Leutic Aortitis (syphilitic)
3) Aortic dissection : extends to coronary Typical angina pain, but coronary arteries are normal on angiography
4) Coronary vaculitis :
Problem in the smaller bracnches of coronary artery, less dialation of
inflammatory lesion in the coronary artery => swelling of the
arteriols
coronary artery wall => impediment to blood flow
- polyarthrtis nodosa
- kwasaki disease
irritation of intima => thrombogenic
5) Coronary artery embolism
- thrombo embolism :mitral stenosis, dilated LA
- infective vegetations infective endocarditis
- fat embolism : severe extensive fat tissue injury, bone injuries,
trouble in pulmonary circulation
6) Polycytemia Hb > 18g/dl Vera ++ : blood is so viscous and it s
movement so slow => static micro circulation that patient may
develop ischemia

7) Severe anemia
8) Carboxyhemoglobulinemia reduced O2 carried by blood
9) Severe chronic lung diseases
 Correlation: pathophysiology => clinical syndromes and complications

Reminder f complications

Inflammation => release of cytokines IL2 TNF => liver => CRP => evaluate the risk of developing MI or reinfarction

Syphilis III involves the wall of aorta vaso vasori destroyed by inflammation => fibrotic process => aorta aneurysm =>

If fibrotic process involves the mouth of coronary arteries => stenotic

Polyarthritis nodosa : PAN many arteries develop necrotic lesions because of antigen deposition (HBs Ag)

 O2 supply +  O2 demand => Relative ischemia

Ischemic heart disease

Angina

MI

Sudden cardiac death

Chronic IHD
Angina
Stable Prinzmetal Unstable NSTEMI STEMI
Coronary artery disease : Atherosclerotic lesions are Coronary artery disease Partially occlusive instable Totally occlusive thrombus
stable atheromatous plaque - not there Unstable plaque => vulnerable plaque (thrombus +) => = :o Severe prolonged ischemia
> 70 % occlusion - not sufficiently obstructive to to acute changes => platelet unstable angina :/ First it starts in the
cause the symptoms plug + thrombogenesis Lasting > 20 min subendocatdial then waves to
=> mural thrombus => partial Prolonged hyotension sub epicardial
Vasospasms obstruction but dynamic events
Pl4 => TxA2 => vasoC
Acute reduction of blood flow
Sub endocardial ischemia Transmural ischemia Sub endocardial ischemia Sub endocardial ischemia
Severe => tachyAr => death < 20 min > 20 min

Angina pain Angina pain Anginal pain

Circumstances : Circumstances : Recent onset
- exertion, emotional stress At rest At rest At rest
- heavy meal More intense and More severe pain More intense and
- walking against cold wind prolonged pain More prolonged but < 20 min more prolonged > 20 min
For a certain degree of exertion may precipitate on emotional effort or at rest
Relives on Relieves ? Relieves? doesn’t relieve on
- taking rest - on rest => no - rest
- or nitrites - on nitrites => yes May not relieve on nitrites - nitrites sometimes even on opioids no relief
Dull, diffuse can be felt only in
the area of radiation
Start substernally or very much
to the left or right it always goes
towards substernal
Radiation
- inner side of arm one or both,
neck, jaw, epigastrium
Pain? Angiography => no clues Severe sympathetic response : tachycardia, sweater, nausea and
patients don t feel the pain vomiting severe process myocardium is dying
Chest discomfort : Auscultation :
- burning sensation - S4 if a big piece is infarcted => dyskinesia => it can t relax well
- heavy pain => atrium has to strongly contract against stiffened ventricle
- pressure - S3 => rapid ventricular filling => cause it is so much dilated
- weight squeezing
Chest Pain S4 => atrial gallop
Males +++ Females +++ S3 => ventricular gallop
Predictable Inpredictable If cardiac failure => somation gallop => S1 2 3 4 with tachycardia
We can use bb in trt : Bb contre indicated
 work =>  demand Use vasoD nitrites Nifedipine
Contre indicates beta blockcers
 1- Angina Stable angina : increased demand on exertion problem
Pain in arm/ radiation : referred pain, usually you get money from
Rest   demands  pain disappears
your father once your mum give you some money you will believe it
s from your dad xD => neurons from C8 => T4 same root value How do nitrites reduce pain?
Ischemic pain
Heavy meal can precipitate ischemic pain : It is not coronary vasoD because
A lot of food => GI tract vasodilation vasodilators mediated =>  1) there is a fixed obstruction that does not dilate
blood flow => GIT exercise => blood rapidely coming to this area 2) coronary stealing : nitrites dilate healthy branches and not stenosed
=>  P in the root of aorta => coronary hypo perfusion one so some blood will be derived from the stenotic to the healthy
If it has atherosclerotic lesions and he is vulnerable to ischemia branches

Chest sensation while walking against cold wind : But Nitrites :

-walking => exersion => heart working more =>  demand
1) general veinoD   EDV  (Starling)   contraction   O2
- cold => arteriolar vasoconstriction => difficult blood flow to skin
demands
=> very difficult to heart to push blood against these narrow
arteriols : total peripheral resistance  => 2) arteriolar dilatation   afterload
HR  :
- heart needs more oxygen it works more =>  O2 needs Prinzmetal angina :
- diastolic time reduces => perfusion time of heart is reduced
Smooth muscles of coronary arteries
and coronary perfusion happens during diastole because during
systole LV strangulates its own microcirculation Normal =>

3types of angina => no net effect of epinephrine on them

- stable typical classical exertional angina
Prinzmetal patients : => spastic tendancy
- prinzmetal angina
- unstable angina ; it anytime it can become MI : pre infarction If we give beta blockers => spasm aggravation

Subclasses of classica le stable angina In Prinzmetal angina nitrites effect is by coronary vasoD

Decubitus angina => severe occlusion 90% => when they lie down =>  Nitrites :
venous return => more work => more O2 demand
- veinoD =>  Preload
Nocturnal angina => suddenly wake up with anginal pain : nightmare =>
+ sympathetic =>  HR => - arterioloD => after load

===> O2 needs reduced In Prinzmetal => coronary vasoD

2. Unstable angina 3. MI
We have to : Infarction => death => biomarkers

- Differenciate it from stable and Prinzmetal angina Symptomatic Vs Silent MI :

More severe more prolonged and may not relieve on nitrites with minimal Silent MI but not silent angina (silent ischemia acceptable)
effort or rest
Angina is pain
- know whether it converted to MI or not
Myocardium can die without pain
It depends on severity and duration of ischemia
Diabetic (neuropathy), transplant heart (denervated heart)
If severe ischemia > 20- 30 min => necrosis
How to diagnose it ?
We prevent conversion of unstable angina => MI by managing the pain
and releasing it before 20 minutes if > 20 minutes => myocytes start dying Myocardial infarction presentations :
=> released - pain
Anginal pain : - non painful:
- on exertion => stable angina -- tachycardia, sweater
- at rest => acute coronary Sd (US, MI ) -- dyspnea, OAP
- < 20 min => US Silent MI
- > 20 min => MI MI

- subendocardial =>partial obstruction

- transmural => Q
Angioplasty preferred than thrombolysis

We have 2 problems : FV => no pulse even though electrical activity is high mechanical is
nothing
Atherom plaque + thrombus
Acute coronary syndrome :
Thrombolysis resolve thrombus only
- unstable angina, subendocardial, transmural angina
But angioplasty gets rid of atheromatous plaque tpp

Another way to manage it : bypass

5. Chronic ischemic heart disease
CCF du LVF
Reperfusion as soon as possible Multiplaques => silent ischemia because repeated attacks of
ischemia => dead myocardial cells
Over years =>
Ischemic cardiomyopathy => fibrotic myocardium
4. Sudden cardiac death
- Unexpected death

- due to cardiac causes

Acute coronary syndrome :

- early or after onset of symptoms or without symptoms within 1 hour 3 things :

- severe obstruction 80-90% + thrombi event => large portion of 1- Classical presentation
myocardium is severly ischemic => severe dysfct => cardiogenic choc 2- ECG
3- Biomarkers of MI
- but they die because of severe FV Additional tests

Ischemic heart => more chances to develop tachyarrythmias

A- ECG : in leads of the territory
1- Hyperacute T wave : release of a lot of K+
2- ST elevation minutes
Normally myocytes depolarize only when they receive Na+ from other 3- T inversion hours
through Gap junctions when cardiac impulse comes 4- Normalization + pathological Q waves => days
Ischemic cell now Q permanent print of infarction
Cations Na+ and Ca++ comes in => mb resting potential fluctuate => Q wave MI => full thikness
arrives to trshold =>
Biomarkers
1- Troponine T and Troponine I
2- CK-mb

1- ECG
2- Biomarkers
3- Echocardiography :
abnormal mvt
cpc => acute MR
thrombus
4- CXR => widening of mediastinum
5- Scintigraphic studies
Technetium 99 => infarcted area => binds ca++ there
Thallium scan => healthy tissue
6- Radionuclide angiography => make blood visible :D in the cavity